Aim: This pilot study explored the feasibility and preliminary effects of a home-based complex exercise programme compared with Pilates in breast cancer survivors with lymphoedema, delivered and assessed remotely via telemedicine. Methods: Participants were non-randomly allocated to Pilates or complex exercise based on recruitment order and preference. Remotely supervised assessments of lymphoedema severity, mobility, and quality of life (QoL) were conducted at baseline and after a 10-week individualised exercise programme. Results: Fourteen participants were included (7 per group), with good adherence and no adverse events. Shoulder range of motion on the affected side increased in both groups (Pilates: +5.3°–11.1°; complex exercise: +6.2°–10.9°). Lower-body mobility findings were mixed: the Pilates group showed consistent within-group improvements in the Chair Sit-and-Reach test (right: +4.5 cm; left: +6.3 cm), whereas between-group effect size estimates tended to favour the complex exercise programme (r = -0.30 to -0.22). On the affected side, limb circumference decreased within the complex exercise group (up to −1.0 cm), with effect size estimates favouring this group (d ≈ 0.6). QoL improved in both groups, with greater improvement in the Health Change domain in the Pilates group, corresponding to a large between-group effect size favouring Pilates (r = -0.62, 95% CI -0.87 to -0.10). Conclusion: These preliminary findings support the feasibility of remotely delivered Pilates and complex exercise programmes and provide effect size estimates to inform the design of future adequately powered randomized controlled trials.

Background Exercise-based rehabilitation is an important component of cancer survivorship care. Circulating microRNAs (miRNAs) have been proposed as potential biomarkers of physiological adaptation; however, their roles in exercise-based cancer rehabilitation remain unclear. This study aimed to explore the potential of candidate miRNAs as biomarkers for evaluating physiologic responses to an exercise-based rehabilitation programme. Methods In this prospective pilot study, 42 cancer survivors were enrolled in a 12-week individualised exercise rehabilitation programme, of whom 24 completed post-intervention assessments. Health-related fitness parameters, including cardiorespiratory capacity, muscle strength, and body composition, were assessed before and after the programme. Plasma levels of muscle- and inflammation-related miRNAs were quantified using quantitative real-time reverse transcription polymerase chain reaction. Results The 12-week exercise programme significantly improved the 6-minute walk distance and muscle strength (p < 0.05). Among the analysed miRNAs, miR-126 showed a significant increase following the intervention. Correlation analyses revealed modest associations between the candidate miRNAs and physiological parameters. Inflammation- and muscle-related miRNAs were strongly correlated, and higher inflammation-related miRNA levels were associated with higher muscle-related miRNA levels. Conclusion The exercise intervention significantly improved functional and physiologic parameters in cancer survivors. Inflammation- and muscle-related miRNAs were correlated at the molecular level. Circulating miRNAs, except for miRNA-126, demonstrated limited responsiveness to the intervention and showed only modest associations with physiological adaptations. Larger and controlled studies are needed to achieve meaningful statistical significance.

Cancer and its treatments often lead to inflammation, muscle problems, and ongoing loss of physical function, as reflected by alterations in circulating microRNAs (miRNAs). In this study, we measured levels of selected muscle- (miR-1, miR-133, miR-208, miR-486, and miR-499) and inflammation-related (miR-21, miR-126, miR-146, and miR-155) miRNAs in breast cancer patients and aimed to explore, using stratified analyses, how their levels relate to cancer subtype, treatment modality, treatment timing, and age. We collected 77 plasma samples from pretreatment and post-treatment breast cancer patients and healthy controls. Circulating miRNA levels were measured using quantitative reverse transcription polymerase chain reaction. We compared miRNA levels across different breast cancer subtypes, treatment modalities, treatment timing, and age groups. Pretreatment patients with breast cancer did not show significant changes in the selected miRNAs compared with healthy controls. However, different breast cancer subtypes showed distinct patterns: Luminal A predominantly affected muscle-related miRNAs, and Luminal B affected inflammation-related miRNAs. Cancer treatment, especially surgery and chemotherapy, led to significant changes in miR-21 and miR-486, primarily within the first 91 days after cancer diagnosis. Increases in miR-133 and miR-486 after treatment were mostly seen in patients over 50 years old. Circulating muscle- and inflammation-related miRNAs display distinct expression patterns associated with breast cancer subtype and treatment. Specifically, miR-21, miR-133, and miR-486 demonstrate sensitivity to cancer treatment exposure, timing, and patient age.

Cancer associated fibroblasts (CAFs) contribute to tumourigenesis and immune tolerance within the tumour microenvironment (TME). Therefore, inhibiting the pro-tumourigenic function of CAFs can be a viable therapeutic approach. However, targeting CAFs is challenging due to the lack of specific markers. The objective of this study is to identify CAF specific therapeutic targets that have the potential to enhance tumour immunity and reduce tumour growth. RNA sequencing was performed on CAFs and normal fibroblasts (NFs) from the same breast cancer patient. Wilms tumour-1 (WT1) was identified as a gene upregulated in CAFs. WT1 levels in CAFs were manipulated using plasmid overexpression of—or siRNA downregulation of WT1. Co-culture assays were performed to evaluate the role of CAF-derived WT1 in T cell proliferation and differentiation using flow cytometry. Western blot and ELISA were performed to interrogate the mechanism of action of WT1 within CAFs. Three-dimensional patient-derived organoids (PDOs) that encompassed the tumour immune-microenvironment were established to determine the therapeutic potential of targeting CAF-derived WT1. WT1, a transcription factor, regulates signal transducer and activator of transcription (STAT) 1/3 levels, promotes programmed death ligand 1 (PD-L1) expression and indoleamine 2,3-dioxygenase (IDO) expression in CAFs. CAF-derived WT1 reduces the proliferation of CD4+ and CD8+ T cells and enhances the differentiation of naïve T cells into regulatory T cells (Tregs), thus producing an immunosuppressive TME. Reducing CAF WT1 levels results in less immunosuppressive CAFs, smaller PDOs and increased levels of cytotoxic granzyme B+ (GZMB+) T cells within the TME. Standard chemotherapeutic agents, paclitaxel (PTX) and doxorubicin (DOX), increase WT1 levels in CAFs enhancing their ability to suppress T cell proliferation. However, Aurantio-obtusin (AO, a DOX analogue) decreases WT1 expression in CAFs reducing their ability to suppress T cell proliferation. AO causes decreased PDO size which correlates with increased levels of T cells within the TME. Therapeutic targeting of the WT1/STAT1/3/PD-L1/IDO axis in CAFs with AO has the potential to enhance T cell activity and reduce Treg percentage within the TME, thereby enhancing tumour immunity and reducing tumourigenesis.

Introduction Primary breast cancer surgery can compromise aesthetics and quality-of-life for breast cancer patients. While breast reconstruction improves these outcomes, current methods are limited by suboptimal aesthetic outcomes and potential complication risks. There is an urgent clinical need for improved approaches to post surgical reconstruction for breast cancer patients. Adipose-derived stromal cells (ADSCs) with biological scaffolds are being widely evaluated for tissue engineering applications in the field of reconstruction. Aims This study aimed to assess the biomechanical properties, biocompatibility, adipogenic potential of ADSCs encapsulated in modified hyaluronic acid derivatives in vitro; and efficacy and tissue integration of this construct in vivo in a murine breast cancer and reconstruction model. Methods ADSCs were obtained, with informed consent, from female breast cancer patients undergoing autologous breast reconstruction or cosmetic procedures (n=8) aged 47±12 years. Modified hyaluronic acid solution was combined with 1×106 ADSCs/mL and crosslinked using hydrogen peroxide and horseradish peroxidase. Young’s modulus, cell viability and adipogenic potential of the cell-loaded hydrogels were assessed in vitro. In vivo, hydrogels combined with murine ADSCs were grafted into a murine breast cancer model and tissues were harvested for immunohistochemistry after 4 weeks. Results ADSCs were characterised via morphology, Colony forming unit-fibroblast (CFU-F) assay, flow cytometry and multilineage differentiation. The cell-loaded hydrogels had a compressive Young’s modulus of 7.35±0.96 kPa after 21 days in culture, similar to human breast adipose tissue (∼10 kPa). High ADSC viability was observed after 21 days in culture, and ADSCs differentiated into mature adipocytes. After 4 weeks in vivo, hydrogels exhibited adipocytes, vascular endothelium, and pericyte-like cells. Conclusion This study demonstrates the potential suitability of modified hyaluronic acid hydrogels encapsulating ADSCs for adipose tissue engineering for post breast cancer reconstruction. ### Competing Interest Statement The authors have declared no competing interest.

Breast cancer is a heterogeneous disease with global reach. Basigin (BSG) is a transmembrane protein with multifunctional roles in the breast tumor microenvironment. Using the hallmarks of cancer, we explore the pleiotropic roles of BSG in breast cancer. Further, we examine the cellular interactants of BSG and the molecular regulators of BSG. BSG has the potential to play a prognostic role and is a candidate target for new therapeutic interventions.

PURPOSE:In Ireland, over 3000 patients are diagnosed with breast cancer annually, and 1 in 9 Irish women will be diagnosed with breast cancer in their lifetime. There is evidence that female breast cancer survivors are more likely to die of cardiovascular disease than their age-matched counterparts. Specific services for cancer patients suffering from cancer therapy related cardiovascular toxicity have led to a higher incidence of safe anti-cancer treatment completion. Such services are not widely available in our jurisdiction, and the purpose of this trial is to remedy this situation. METHODS:This protocol describes a prospective, single arm, pilot feasibility study implementing a dedicated Cardio-Oncology assessment and surveillance pathway for patients receiving multimodal breast cancer treatment. It incorporates novel biomarker and radiomic surveillance and monitoring approaches for cancer-therapy related cardiac dysfunction into routine care for breast cancer patients undergoing adjuvant systemic chemotherapy. RESULTS:Declaration of results will via peer reviewed academic journals, and communicated directly to key knowledge users both nationally and internationally. This engagement will be critical to enable to healthcare services and policy sector make informed decisions or valuable changes to clinical practice, expenditure and/or systems development to support specialized Cardio-Oncology clinical pathways. All data is to be made available upon request. CONCLUSION:Dedicated cardio-oncology services have been recommended in recent literature to improve patient outcomes. Our protocol describes a feasibility study into the provision of such services for breast cancer.

Background: Sarcopenia has been associated with negative clinical outcomes in several cancers, however its prevalence and impact on outcomes in patients being treated for locally advanced breast cancer (LABC) are yet to be determined. We assessed the impact of sarcopenia on outcomes in LABC. Methods: Consecutive female patients with LABC indicated to undergo neoadjuvant therapy (NAT) and surgery between 2010–2015 were included. Skeletal muscle index (SMI) and lean body mass (LBM) were determined. Sarcopenia was defined using computed tomography (CT) at L3 as SMI <38.5 cm2/m2. Thereafter, multivariable linear, logistic, and Cox regression analysis was undertaken to determine the independent impact of sarcopenia on outcomes. Results: Among 258 patients, the prevalence of sarcopenia was 23.0%, 7.8% and 0.0% of patients with normal weight, overweight and obesity, respectively (P=0.001). Sarcopenia was not associated with cT and cN stage, tumour grade, histologic type or receptor status. Moreover, sarcopenia was not associated with tumour sensitivity to NAT (i.e., ypT and ypN stage, pathologic complete response, and Sataloff grade). Postoperatively, sarcopenia did not independently predict with comprehensive complications index (P=0.242), length of stay (P=0.716) or overall morbidity (P=0.365). However, on multivariable analysis, lower LBM independently predicted reduced invasive disease-free survival (iDFS) [hazard ratio (HR): 0.93, 95% confidence interval (CI): 0.87–1.00, P=0.049] and overall survival (OS) (HR: 0.92, 95% CI: 0.85–0.99, P=0.028), but not disease-specific survival (DSS) (P=0.070). Conclusions: Sarcopenia was not associated with clinicopathological parameters or tumour response to NAT, however, reduced LBM independently predicted OS, but not DSS, in LABC. These data suggest that the prognostic impact of sarcopenia may be largely mediated by impaired performance status and increased non-cancer mortality.

Background Tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) inhibitor pathway with immune checkpoint blockade have shown promising outcomes in managing metastatic renal cancer. However, they increase the risk of a person developing high blood pressure and cardiovascular complications. Case summary In this study, we report the case of a 73-year-old woman on axitinib and pembrolizumab for her Stage 4 renal cell carcinoma. She presented with intractable chest pain and high systolic blood pressure, not responding to opiates. Her computed tomography angiography results showed an acute intra-mural haematoma with a rupture in the descending thoracic aorta. She underwent emergency thoracic endovascular aortic repair. Post-operatively, she recovered fully without any neurological or cardiovascular issues. Discussion The severity of cardiovascular haemodynamic complications arising from the consumption of VEGF inhibitors and from immunotherapy and the lack of anti-hypertensive strategies to adequately manage such events require an unequivocal and urgent assessment of their cardiovascular safety. This case highlights the crucial role of cardiovascular oncology in managing such acute aortic catastrophes.

Breast cancer is amongst the most common invasive cancers in adults. There are established relationships between anti-cancer treatments for breast cancer and cardiovascular side effects. In recent years, novel anti-cancer treatments have been established, as well as the availability of multi-modal cardiac imaging and the sophistication of treatment for cardiac disease. This review provides an in-depth overview regarding the interface of breast cancer and cancer therapy-related cardiovascular toxicity. Specifically, it reviews the pathophysiology of breast cancer, the method of action in therapy-related cardiovascular toxicity from anti-cancer treatment, the use of echocardiography, cardiac CT, MRI, or nuclear medicine as diagnostics, and the current evidence-based treatments available. It is intended to be an all-encompassing review for clinicians caring for patients in this situation.

Cardiac biomarkers are a vital component within the first edition of the European Society of Cardiology guidelines in Cardio-Oncology. Specifically, they are mentioned in the definition of mild asymptomatic cancer therapy-related cardiac dysfunction, where left ventricular systolic function is ≥50 % with two outcomes; either a new decrease in global longitudinal strain >15 % from baseline and/or a new rise in cardiac biomarkers above the defined 99th percentile cut off values. Cardiac troponin is one such biomarker. Many of the treatments for breast cancer have published data on cardiac dysfunction and/or cardiovascular toxicity, and such may lead to an elevation in cardiac troponin. However, there is conflicting and incomplete data regarding how to approach an elevated cardiac troponin during anti-cancer treatment, which has confounded patient care in the clinical trial setting. We propose a novel framework to guide physicians in treatment-related elevation of cardiac troponin in the breast cancer population. Secondly, the additive role which the recommendation that cardiac troponin carries within mild asymptomatic definitions of CTRCD is the subject of great debate. We suggest a reflection on the role of biomarkers, specifically in reference to cardiac troponin.

PDF file, 107K, Summary characteristics of the participating BCAC case-control studies.